Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans

AbstractNociceptive neurons innervate the skin with complex dendritic arbors that respond to pain-evoking stimuli such as harsh mechanical force or extreme temperatures. Here we describe the structure and development of a model nociceptor, the PVD neuron of C. elegans, and identify transcription factors that control morphogenesis of the PVD dendritic arbor. The two PVD neuron cell bodies occupy positions on either the right (PVDR) or left (PVDL) sides of the animal in posterior–lateral locations. Imaging with a GFP reporter revealed a single axon projecting from the PVD soma to the ventral cord and an elaborate, highly branched arbor of dendritic processes that envelop the animal with a web-like array directly beneath the skin. Dendritic branches emerge in a step-wise fashion during larval development and may use an existing network of peripheral nerve cords as guideposts for key branching decisions. Time-lapse imaging revealed that branching is highly dynamic with active extension and withdrawal and that PVD branch overlap is prevented by a contact-dependent self-avoidance, a mechanism that is also employed by sensory neurons in other organisms. With the goal of identifying genes that regulate dendritic morphogenesis, we used the mRNA-tagging method to produce a gene expression profile of PVD during late larval development. This microarray experiment identified>2,000 genes that are 1.5X elevated relative to all larval cells. The enriched transcripts encode a wide range of proteins with potential roles in PVD function (e.g., DEG/ENaC and Trp channels) or development (e.g., UNC-5 and LIN-17/frizzled receptors). We used RNAi and genetic tests to screen 86 transcription factors from this list and identified eleven genes that specify PVD dendritic structure. These transcription factors appear to control discrete steps in PVD morphogenesis and may either promote or limit PVD branching at specific developmental stages. For example, time-lapse imaging revealed that MEC-3 (LIM homeodomain) is required for branch initiation in early larval development whereas EGL-44 (TEAD domain) prevents ectopic PVD branching in the adult. A comparison of PVD-enriched transcripts to a microarray profile of mammalian nociceptors revealed homologous genes with potentially shared nociceptive functions. We conclude that PVD neurons display striking structural, functional and molecular similarities to nociceptive neurons from more complex organisms and can thus provide a useful model system in which to identify evolutionarily conserved determinants of nociceptor fate

North to south: ecosystem features determine seagrass community response to sea otter foraging

We compared sea otter recovery in California (CA) and British Columbia (BC) to determine how key ecosystem properties shape top-down effects in seagrass communities. Potential ecosystem drivers of sea otter foraging in CA and BC seagrass beds that we examined include the role of coastline complexity and environmental stress on sea otter effects. In BC, we found greater species richness across seagrass trophic assemblages. Furthermore, Cancer spp. crabs, an important link in the seagrass trophic cascade observed in CA, was less common. Additionally, the more recent reintroduction of sea otters, more complex coastline, and reduced environmental stress in BC seagrass habitats supported the hypothesis that sea otter foraging pressure is currently reduced in more northern latitudes. In order to manage the ecosystem features that lead to regional differences in top predator effects in seagrass communities, we review our findings, their spatial and temporal constraints, and present a social-ecological framework for future re- search

Predictors of posttraumatic stress symptom trajectories in parents of children exposed to motor vehicle collisions

Following child trauma, parents are at risk of developing posttraumatic stress disorder (PTSD), either owing to their direct involvement or from hearing of their child's involvement. Despite the potential impact of a parent's development of PTSD on both the parent and child, little is known about what may place a parent at increased risk.   METHOD: PTSD symptoms were assessed ≤4 weeks, 6 months, and 3 years post-trauma, along with a range of potential risk factors, in a sample of parents of 2-10-year-old children who were involved in a motor vehicle collision.   RESULTS AND CONCLUSIONS: Two symptom trajectories were identified: Those parents whose symptoms remained low across all time points and those whose symptoms remained elevated at 6 months post-trauma and declined by 3 years. Subjective threat, thought suppression, and maladaptive cognitions about damage to the child were identified as key predictors of poorer outcomes

Cognitive therapy as an early treatment for post-traumatic stress disorder in children and adolescents: a randomized controlled trial addressing preliminary efficacy and mechanisms of action.

BACKGROUND: Few efficacious early treatments for post-traumatic stress disorder (PTSD) in children and adolescents exist. Previous trials have intervened within the first month post-trauma and focused on secondary prevention of later post-traumatic stress; however, considerable natural recovery may still occur up to 6-months post-trauma. No trials have addressed the early treatment of established PTSD (i.e. 2- to 6-months post-trauma). METHODS: Twenty-nine youth (8-17 years) with PTSD (according to age-appropriate DSM-IV or ICD-10 diagnostic criteria) after a single-event trauma in the previous 2-6 months were randomly allocated to Cognitive Therapy for PTSD (CT-PTSD; n = 14) or waiting list (WL; n = 15) for 10 weeks. RESULTS: Significantly more participants were free of PTSD after CT-PTSD (71%) than WL (27%) at posttreatment (intent-to-treat, 95% CI for difference .04-.71). CT-PTSD yielded greater improvement on child-report questionnaire measures of PTSD, depression and anxiety; clinician-rated functioning; and parent-reported outcomes. Recovery after CT-PTSD was maintained at 6- and 12-month posttreatment. Beneficial effects of CT-PTSD were mediated through changes in appraisals and safety-seeking behaviours, as predicted by cognitive models of PTSD. CT-PTSD was considered acceptable on the basis of low dropout and high treatment credibility and therapist alliance ratings. CONCLUSIONS: This trial provides preliminary support for the efficacy and acceptability of CT-PTSD as an early treatment for PTSD in youth. Moreover, the trial did not support the extension of 'watchful waiting' into the 2- to 6-month post-trauma window, as significant improvements in the WL arm (particularly in terms of functioning and depression) were not observed. Replication in larger samples is needed, but attention to recruitment issues will be required

Resolution of the type material of the Asian elephant, Elephas maximus Linnaeus, 1758 (Proboscidea, Elephantidae)

The understanding of Earth’s biodiversity depends critically on the accurate identification and nomenclature of species. Many species were described centuries ago, and in a surprising number of cases their nomenclature or type material remain unclear or inconsistent. A prime example is provided by Elephas maximus, one of the most iconic and well-known mammalian species, described and named by Linnaeus (1758) and today designating the Asian elephant. We used morphological, ancient DNA (aDNA), and high-throughput ancient proteomic analyses to demonstrate that a widely discussed syntype specimen of E. maximus, a complete foetus preserved in ethanol, is actually an African elephant, genus Loxodonta. We further discovered that an additional E. maximus syntype, mentioned in a description by John Ray (1693) cited by Linnaeus, has been preserved as an almost complete skeleton at the Natural History Museum of the University of Florence. Having confirmed its identity as an Asian elephant through both morphological and ancient DNA analyses, we designate this specimen as the lectotype of E. maximus

An Alternative Approach to Nucleic Acid Memory

DNA is a compelling alternative to non-volatile information storage technologies due to its information density, stability, and energy efficiency. Previous studies have used artificially synthesized DNA to store data and automated next-generation sequencing to read it back. Here, we report digital Nucleic Acid Memory (dNAM) for applications that require a limited amount of data to have high information density, redundancy, and copy number. In dNAM, data is encoded by selecting combinations of single-stranded DNA with (1) or without (0) docking-site domains. When self-assembled with scaffold DNA, staple strands form DNA origami breadboards. Information encoded into the breadboards is read by monitoring the binding of fluorescent imager probes using DNA-PAINT super-resolution microscopy. To enhance data retention, a multi-layer error correction scheme that combines fountain and bi-level parity codes is used. As a prototype, fifteen origami encoded with ‘Data is in our DNA!\n’ are analyzed. Each origami encodes unique data-droplet, index, orientation, and error-correction information. The error-correction algorithms fully recover the message when individual docking sites, or entire origami, are missing. Unlike other approaches to DNA-based data storage, reading dNAM does not require sequencing. As such, it offers an additional path to explore the advantages and disadvantages of DNA as an emerging memory material

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Author version made available in accordance with publisher policy.Abstract Background The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett’s esophagus. Methods Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett’s esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett’s esophagus (Mann-Whitney U test, P<0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett’s esophagus (linear regression, P0.7, P<0.05). A multi-biomarker panel (RNU6-1/miR- 16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR- 30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC=0.99, 95 % CI 0.96–1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett’s esophagus. Conclusions This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma

Restoring habitat for fire-impacted species' across degraded Australian landscapes

In the summer of 2019-2020, southern Australia experienced the largest fires on record, detrimentally impacting the habitat of native species, many of which were already threatened by past and current anthropogenic land use. A large-scale restoration effort to improve degraded species habitat would provide fire-affected species with the chance to recover and persist in burnt and unburnt habitat. To facilitate this, decision-makers require information on priority species needs for restoration intervention, the suite of potential restoration interventions, and the priority locations for applying these interventions. We prioritize actions in areas where restoration would most likely provide cost-effective benefits to priority species (defined by each species proportion of habitat burned, threat status, and vulnerability to fires), by integrating current and future species habitat suitability maps with spatially modelled costs of restoration interventions such as replanting, removing invasive species, and implementing ecologically appropriate fire management. We show that restoring the top similar to 69% (112 million hectares) of the study region (current and future distributions of priority species) accounts for, on average, 95% of current and future habitat for every priority species and costs similar to AUD$73 billion yr(-1) (AUD$650 hectare(-1) yr(-1)) annualized over 30 years. This effort would include restoration actions over 6 million hectares of fire-impacted habitat, costing similar to AUD$8.8 billion/year. Large scale restoration efforts are often costly but can have significant societal co-benefits beyond biodiversity conservation. We also show that up to 291 MtCO2 (similar to 150 Mt DM) of carbon could be sequestered by restoration efforts, resulting in approximately AUD$253 million yr(-1) in carbon market revenue if all carbon was remunerated. Our approach highlights the scale, costs, and benefits of targeted restoration activities both inside and outside of the immediate bushfire footprint over vast areas of different land tenures